SAR113945 monopotassium is a highly selective IKK-β inhibitor with an IC50 value of 0.4 nM. SAR113945 monopotassium blocks the canonical NFκB signaling pathway. SAR113945 monopotassium alleviates hyperalgesia to heat and mechanical stimuli, and exerts effects in a zymosan-induced knee joint inflammation model. SAR113945 monopotassium is applicable to research related to symptomatic knee osteoarthritis [1] [2] [3].
In Vivo, SAR113945 (0.01-10 mg per joint; intra-articular; single dose) monopotassium produces statistically significant dose-dependent pain reduction in a zymosan-induced inflammatory knee joint pain model in male Lewis rats, with an 88% maximum pain reduction at the 10 mg per joint dose[1].
In Vitro, SAR113945 monopotassium potently inhibits the native IKK complex purified from HeLa cell extracts, with an IC50 of 0.018 μM[1]. SAR113945 (10 μM) monopotassium exhibits high kinase specificity. In a kinome panel comprising 62 kinases, it only inhibits mixed lineage kinase 1 (MLK1) by 59% at a concentration of 10 μM[1]. SAR113945 (10 μM) monopotassium exhibits high receptor and enzyme specificity, acting solely as an antagonist of the adenosine A3 receptor, with an IC50 of 0.89 μM in a screening panel comprising 106 targets[1]. SAR113945 (Compound 1) monopotassium inhibits IKK-β with an IC50 of 0.4 nM[3].
References:
[1]. Grothe K, et al. IκB kinase inhibition as a potential treatment of osteoarthritis - results of a clinical proof-of-concept study. Osteoarthritis Cartilage. 2017 Jan;25(1):46-52.
[2]. Liu D, et al. Small molecule inhibitors of osteoarthritis: Current development and future perspective. Frontiers in physiology. 2023;14:1156913.
[3]. Noha SM, et al. Discovery of a novel IKK-β inhibitor by ligand-based virtual screening techniques. Bioorganic & medicinal chemistry letters. 2011 Jan 01;21(1):577-83.
In Vivo, SAR113945 (0.01-10 mg per joint; intra-articular; single dose) monopotassium produces statistically significant dose-dependent pain reduction in a zymosan-induced inflammatory knee joint pain model in male Lewis rats, with an 88% maximum pain reduction at the 10 mg per joint dose[1].
In Vitro, SAR113945 monopotassium potently inhibits the native IKK complex purified from HeLa cell extracts, with an IC50 of 0.018 μM[1]. SAR113945 (10 μM) monopotassium exhibits high kinase specificity. In a kinome panel comprising 62 kinases, it only inhibits mixed lineage kinase 1 (MLK1) by 59% at a concentration of 10 μM[1]. SAR113945 (10 μM) monopotassium exhibits high receptor and enzyme specificity, acting solely as an antagonist of the adenosine A3 receptor, with an IC50 of 0.89 μM in a screening panel comprising 106 targets[1]. SAR113945 (Compound 1) monopotassium inhibits IKK-β with an IC50 of 0.4 nM[3].
References:
[1]. Grothe K, et al. IκB kinase inhibition as a potential treatment of osteoarthritis - results of a clinical proof-of-concept study. Osteoarthritis Cartilage. 2017 Jan;25(1):46-52.
[2]. Liu D, et al. Small molecule inhibitors of osteoarthritis: Current development and future perspective. Frontiers in physiology. 2023;14:1156913.
[3]. Noha SM, et al. Discovery of a novel IKK-β inhibitor by ligand-based virtual screening techniques. Bioorganic & medicinal chemistry letters. 2011 Jan 01;21(1):577-83.